The long-term goal of this application is the understanding of the mechanisms of thyroid hormone (T3) action with focus on the roles of T3 receptors (TR) in the regulation of gene expression. The specific aims of this application are to: (1) identify TR amino acids required specifically for both the formation of heterodimers between TRs and the retinoid X receptors (RXRs), and for transcriptional activation by such heterodimeric complexes; (2) identify new proteins that interact specifically with TRs in the presence and absence of T3, and characterize their roles in TR function; and (3) define the in vivo occupancy of T3 and other response elements by TRs and other members of the nuclear hormone receptor superfamily.